title: Phase-I/II radio-immunotherapy study with Iodine-131-labeled anti-CEA monoclonal antibody F6 F(ab')2 in patients with non-resectable liver metastases from colorectal cancer.
abstract: Experimental studies in nude mice with human colon-carcinoma grafts demonstrated the therapeutic efficiency of F(ab')2 fragments to carcinoembryonic antigen (CEA) labeled with a high dose of 131Iodine. A phase I/II study was designed to determine the maximum tolerated dose of 131I-labeled F(ab')2 fragments (131I-F(ab')2) from anti-CEA monoclonal antibody F6, its limiting organ toxicity and tumor uptake. Ten patients with non-resectable liver metastases from colorectal cancer (9 detected by CT scan and 1 by laparotomy) were treated with 131I-F(ab')2, doses ranging from 87 mCi to 300 mCi for the first 5 patients, with a constant 300-mCi dose for the last 5 patients. For all the patients, autologous bone marrow was harvested and stored before treatment. Circulating CEA ranged from 2 to 126 ng/ml. No severe adverse events were observed during or immediately following infusion of therapeutic doses. The 9 patients with radiologic evidence of liver metastases showed uptake of 131I-F(ab')2 in the metastases, as observed by single-photon-emission tomography. The only toxicity was hematologic, and no severe aplasia was observed when up to 250 mCi was infused. At the 300-mCi dose, 5 out of 6 patients presented grade-3 or -4 hematologic toxicity, with a nadir for neutrophils and thrombocytes ranging from 25 to 35 days after infusion. In these 5 cases, bone marrow was re-infused. No clinical complications were observed during aplasia. The tumor response could be evaluated in 9 out of 10 patients. One patient showed a partial response of one small liver metastasis (2 cm in diameter) and a stable evolution of the other metastases, 2 patients had stable disease, and 6 showed tumor progression at the time of evaluation (2 or 3 months after injection) by CT scan. This phase-I/II study demonstrated that a dose of 300 mCi of 131I-F(ab')2 from the anti-CEA Mab F6 is well tolerated with bone-marrow rescue, whereas a dose of 200 mCi can be infused without severe bone-marrow toxicity.
authors.affiliation: Val d'Aurelle-Paul Lamarque Cancer Center, Montpellier, France. MYCHOU@valdorel.fnclcc.fr
authors.forename: M
authors.initials: M
authors.lastname: Ychou
authors.forename: A
authors.initials: A
authors.lastname: Pelegrin
authors.forename: P
authors.initials: P
authors.lastname: Faurous
authors.forename: B
authors.initials: B
authors.lastname: Robert
authors.forename: J C
authors.initials: JC
authors.lastname: Saccavini
authors.forename: D
authors.initials: D
authors.lastname: Guerreau
authors.forename: J F
authors.initials: JF
authors.lastname: Rossi
authors.forename: M
authors.initials: M
authors.lastname: Fabbro
authors.forename: F
authors.initials: F
authors.lastname: Buchegger
authors.forename: J P
authors.initials: JP
authors.lastname: Mach
authors.forename: J C
authors.initials: JC
authors.lastname: Artus
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006410:Hematopoiesis; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000556:secondary* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016499:Radioimmunotherapy / Q000009:adverse effects / Q000379:methods*
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes